Optic atrophy 1 mediates muscle differentiation by promoting a metabolic switch via the supercomplex assembly factor SCAF1

Autor: Matthew Triolo, Nicole Baker, Soniya Agarwal, Nikita Larionov, Tina Podinić, Mireille Khacho
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 3, Pp 109164- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109164
Popis: Summary: Myogenic differentiation is integral for the regeneration of skeletal muscle following tissue damage. Though high-energy post-mitotic muscle relies predominantly on mitochondrial respiration, the importance of mitochondrial remodeling in enabling muscle differentiation and the players involved are not fully known. Here we show that the mitochondrial fusion protein OPA1 is essential for muscle differentiation. Our study demonstrates that OPA1 loss or inhibition, through genetic and pharmacological means, abolishes in vivo muscle regeneration and in vitro myotube formation. We show that both the inhibition and genetic deletion of OPA1 prevent the early onset metabolic switch required to drive myoblast differentiation. In addition, we observe an OPA1-dependent upregulation of the supercomplex assembly factor, SCAF1, at the onset of differentiation. Importantly, preventing the upregulation of SCAF1, through OPA1 loss or siRNA-mediated SCAF1 knockdown, impairs metabolic reprogramming and muscle differentiation. These findings reveal the integral role of OPA1 and mitochondrial reprogramming at the onset of myogenic differentiation.
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